Skin wound healing is coordinated by a delicate balance between proinflammatory and anti-inflammatory responses, which can be affected by opportunistic pathogens and metabolic or vascular diseases. Several antimicrobial peptides (AMPs) possess immunomodulatory properties, suggesting their potential to support skin wound healing. Here, we evaluated the proregenerative activity of three recently described AMPs (Clavanin A, Clavanin-MO, and Mastoparan-MO). Human primary dermal fibroblasts (hFibs) were used to determine peptide toxicity and their capacity to induce cell proliferation and migration. Furthermore, mRNA analysis was used to investigate the modulation of genes associated with skin regeneration. Subsequently, the regenerative potential of the peptides was further confirmed using an ex vivo organotypic model of human skin (hOSEC)-based lesion. Our results indicate that the three molecules evaluated in this study have regenerative potential at nontoxic doses (i.e., 200 μM for Clavanin-A and Clavanin-MO, and 6.25 μM for Mastoparan-MO). At these concentrations, all peptides promoted the proliferation and migration of hFibs during in vitro assays. Such processes were accompanied by gene expression signatures related to skin regenerative processes, including significantly higher KI67, HAS2 and CXCR4 mRNA levels induced by Clavanin A and Mastoparan-MO. Such findings translated into significantly accelerated wound healing promoted by both Clavanin A and Mastoparan-MO in hOSEC-based lesions. Overall, the data demonstrate the proregenerative properties of these peptides using human experimental skin models, with Mastoparan-MO and Clavanin A showing much greater potential for inducing wound healing compared to Clavanin-MO.

Osteosarcoma (OS) is the most common primary malignant bone sarcoma among children and adolescents. Treatment is based on neo-adjuvant and adjuvant chemotherapy, using the standard drugs cisplatin, methotrexate, doxorubicin, and ifosfamide (IFO). Due to the high capacity of tumor resistance, the current work aimed to analyze genes related to cycle control and cell differentiation in OS cells sensitive to and with induced resistance to IFO. This was to assess whether the differentiated expression of these genes may affect resistance to the drug IFO used in OS treatment, and thus establish possible biomarkers of disease progression. In this work, the treatment-sensitive OS U2OS lineage was used, and the same lineage was submitted to the process of induction of IFO resistance. These cells were evaluated by MTT, migration and proliferation assays and submitted to gene expression analysis. The results demonstrate that after induction of resistance to IFO, resistant U2OS cells show a more aggressive tumor behavior, with greater capacity for cell migration, proliferation, and invasion compared to sensitive cells. Gene analysis indicates that resistance-induced cells have differentiated expression of the genes EPB41L3, GADD45A, IER3, OXCT1, UBE2L6, UBE2A ALPL, and EFNB2. Our results suggest new perspectives on possible resistance biomarkers, especially the genes EFNB2 and EPB41L3, given that these genes have rarely been studied their expression linked to osteosarcoma. They show how the resistance induction model can be useful for studies on tumor cell behavior.

Chronic kidney disease (CKD) is a global health problem, especially in the elderly, leading to renal failure through gradual progression and chronic inflammation, in addition to increasing cardiovascular risk. MicroRNAs (miRNAs), non-coding RNAs that regulate gene expression, act as chemical messengers and have been shown to be important for the diagnosis and prognosis of chronic diseases. This study investigates miRNAs such as miR-1, miR-16, miR-150 and miR-206, involved in inflammatory and cardiovascular processes in patients with end-stage renal disease (ESRD). The objective was to evaluate the association of these miRNAs with cardiovascular risk factors, inflammatory status and physical-functional capacity. 23 individuals without CKD (control) and 25 with ESRD were selected. The results showed that the expressions of miRNAs and tumor necrosis factor alpha are higher in patients with ESRD, while fat-free mass, handgrip strength and functional capacity are reduced. All miRNAs analyzed showed a positive correlation with the inflammatory state and a negative correlation with physical-functional capacity. The miR-16 and miR-206 stood out in the study, supporting the potential role of these miRNAs, especially miR-16, as exploratory biomarkers associated with ESRD-related inflammatory and physical-functional impairment. Thus, the work contributes significantly to the development of more targeted and individualized therapeutic interventions, promoting significant advances in the care of ESRD and its complications.